Two siblings with non-classic P450scc deficiency resulted from a novel mutation in CYP11A1 gene misdiagnosed as familial glucocorticoid deficiency

Abstract

P450scc deficiency due to CYP11A1 gene mutations is a rare cause of primary adrenal insufficiency (PAI) in children. We reported two young siblings with PAI presented with hyperpigmentation. They were referred to our clinic with a diagnosis of familial glucocorticoid deficiency (FGD), another rare cause of PAI. However, further hormonal evaluation revealed increased plasma renin activity, which was not congruent with the diagnosis of FGD. Genetic analysis showed the compound heterozygous mutations in exon 8 of the CYP11A1 gene, including a missense mutation, R466W (c1396C>T), and a nonsense mutation, R439X (c1315C>T). A case responded well to hydrocortisone, while another case received prednisolone due to her unresponsiveness to hydrocortisone. To correctly diagnose P450scc deficiency, physicians should be alerted with the similarity between this disease and FGD because of their predominant glucocorticoid deficiency. Long-acting glucocorticoids may be used with caution to reach treatment goals.

Keywords: Endocrine system; Genetics; Paediatrics (drugs and medicines).